Human papillomavirus (HPV) is the most common viral sexually transmitted disease (STD) and has been implicated in the majority of anogenital malignancies. The study of the epidemiology of HPV is hampered by the inability to grow the virus in the laboratory and the lack of an animal model. The current "gold-standard" of infection is the detection of HPV DNA in anogenital specimens by PCR or hybridization techniques. These techniques have noted an association of the detection of HPV DNA with the increased numbers of sexual partners. However, these techniques require an extensive physical examination, i.e. pelvic, and are not applicable to large population epidemiologic surveys. Due to the lack of an adequate antigen source, serological assays for HPV are not widely available. Recently, in-vitro production of HPV capsids of numerous types using various expression systems have yielded a source of antigen to develop immunoassays for the detection of HPV specific antibodies. These assays have identified human IgG responses that react to type-specific, conformational epitopes of the major capsid protein and the presence of HPV capsid antibodies are associated with the detection of HPV DNA and HPV-related disease. These serum tests can now be used to screen larger populations at potential risk for HPV-related disease. Although this represents a tremendous advance in the epidemiology of anogenital malignancies, there are populations at risk where serum screening is difficult. Adolescents and other children who are potentially at risk for acquiring HPV infection may have been exposed and have HPV-specific antibodies, but the acquisition of serum from these individuals has traditionally been difficult. Therefore, there needs to be a means by which at-risk individuals can be screened for HPV antibodies in a less invasive manner. Numerous antibodies against viral pathogens (hepatitis, measles, mumps, rubella, parvovirus, and HIV) have been detected in oral fluids and reliably reflect the serum status of these individuals. We hypothesize that HPV capsid IgG antibodies can be detected in oral fluids and that the detection of these antibodies will be reflective of that in serum of these patients. We propose to simultaneously collect serum, expectorated saliva and oral mucosa transudate from 900 subjects who are at high risk for HPV infection and test these samples for antibodies to HPV types 6/11, 16,18, 31, and 45 using a well-characterized capture ELISA. This proposal will lay the groundwork for the application of a saliva test to perform large epidemiological surveys and better define the populations at risk for HPV infection and disease.